SVD identifies transcript length distribution functions from DNA microarray data and reveals evolutionary forces
Nicolas M Bertagnolli1, Justin A Drake, Jason M Tennessen
1Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, United States of America ; Department of Bioengineering, University of Utah, Salt Lake City, Utah, United States of America.
Evolutionary forces shape transcript length. Shorter transcripts are linked to protein synthesis and mitochondrial metabolism, while longer ones are associated with glucose metabolism, impacting tumor development.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Bioinformatics
Background:
- Transcript length is a fundamental characteristic of genes.
- Understanding the evolutionary pressures on transcript length is crucial for deciphering gene regulation.
- Previous hypotheses suggested evolutionary forces, akin to a harmonic oscillator, influence transcript length.
Purpose of the Study:
- To identify evolutionary forces acting on transcript length.
- To investigate the relationship between transcript length, gene ontology, and cellular metabolism.
- To explore transcript length regulation in normal versus glioblastoma multiforme (GBM) tissues.
Main Methods:
- Singular Value Decomposition (SVD) applied to DNA microarray data to determine transcript length distribution functions.
- Comparison of transcript length distributions across gene ontology annotations in human and yeast.
- Analysis of transcript length differences in GBM versus normal brain tissue using The Cancer Genome Atlas data.
Main Results:
- SVD successfully identified transcript length distribution functions as "asymmetric generalized coherent states" without prior assumptions.
- Transcripts involved in protein synthesis and mitochondrial metabolism are significantly shorter than those in glucose metabolism across human and yeast.
- Glioblastoma multiforme (GBM) exhibits altered transcript length regulation, favoring shorter transcripts for protein synthesis/mitochondrial metabolism and suppressing longer ones for glucose metabolism/brain activity.
Conclusions:
- Transcript length is significantly correlated with cellular functions like metabolism and gene ontology.
- Differential regulation of transcript length may represent a physical mechanism for metabolic control in normal and tumor cells.
- Findings support evolutionary models proposing harmonic oscillator-like forces shaping transcript length.
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